Commensal microbe-derived butyrate induces the differentiation of colonic regulatory T cells - PubMed (original) (raw)
. 2013 Dec 19;504(7480):446-50.
doi: 10.1038/nature12721. Epub 2013 Nov 13.
Yuuki Obata 2, Shinji Fukuda 3, Takaho A Endo 4, Gaku Nakato 4, Daisuke Takahashi 4, Yumiko Nakanishi 5, Chikako Uetake 4, Keiko Kato 6, Tamotsu Kato 4, Masumi Takahashi 4, Noriko N Fukuda 5, Shinnosuke Murakami 5, Eiji Miyauchi 4, Shingo Hino 7, Koji Atarashi 8, Satoshi Onawa 4, Yumiko Fujimura 9, Trevor Lockett 10, Julie M Clarke 10, David L Topping 10, Masaru Tomita 5, Shohei Hori 4, Osamu Ohara 4, Tatsuya Morita 7, Haruhiko Koseki 11, Jun Kikuchi 12, Kenya Honda 13, Koji Hase 14, Hiroshi Ohno 11
Affiliations
- PMID: 24226770
- DOI: 10.1038/nature12721
Commensal microbe-derived butyrate induces the differentiation of colonic regulatory T cells
Yukihiro Furusawa et al. Nature. 2013.
Erratum in
- Nature. 2014 Feb 13;506(7487):254
Abstract
Gut commensal microbes shape the mucosal immune system by regulating the differentiation and expansion of several types of T cell. Clostridia, a dominant class of commensal microbe, can induce colonic regulatory T (Treg) cells, which have a central role in the suppression of inflammatory and allergic responses. However, the molecular mechanisms by which commensal microbes induce colonic Treg cells have been unclear. Here we show that a large bowel microbial fermentation product, butyrate, induces the differentiation of colonic Treg cells in mice. A comparative NMR-based metabolome analysis suggests that the luminal concentrations of short-chain fatty acids positively correlates with the number of Treg cells in the colon. Among short-chain fatty acids, butyrate induced the differentiation of Treg cells in vitro and in vivo, and ameliorated the development of colitis induced by adoptive transfer of CD4(+) CD45RB(hi) T cells in Rag1(-/-) mice. Treatment of naive T cells under the Treg-cell-polarizing conditions with butyrate enhanced histone H3 acetylation in the promoter and conserved non-coding sequence regions of the Foxp3 locus, suggesting a possible mechanism for how microbial-derived butyrate regulates the differentiation of Treg cells. Our findings provide new insight into the mechanisms by which host-microbe interactions establish immunological homeostasis in the gut.
Comment in
- Mucosal immunology: Bacteria get T(Reg) cells into shape.
Kugelberg E. Kugelberg E. Nat Rev Immunol. 2014 Jan;14(1):2-3. doi: 10.1038/nri3583. Epub 2013 Nov 29. Nat Rev Immunol. 2014. PMID: 24287865 No abstract available.
Similar articles
- Metabolites produced by commensal bacteria promote peripheral regulatory T-cell generation.
Arpaia N, Campbell C, Fan X, Dikiy S, van der Veeken J, deRoos P, Liu H, Cross JR, Pfeffer K, Coffer PJ, Rudensky AY. Arpaia N, et al. Nature. 2013 Dec 19;504(7480):451-5. doi: 10.1038/nature12726. Epub 2013 Nov 13. Nature. 2013. PMID: 24226773 Free PMC article. - Microbiota-derived butyrate limits the autoimmune response by promoting the differentiation of follicular regulatory T cells.
Takahashi D, Hoshina N, Kabumoto Y, Maeda Y, Suzuki A, Tanabe H, Isobe J, Yamada T, Muroi K, Yanagisawa Y, Nakamura A, Fujimura Y, Saeki A, Ueda M, Matsumoto R, Asaoka H, Clarke JM, Harada Y, Umemoto E, Komatsu N, Okada T, Takayanagi H, Takeda K, Tomura M, Hase K. Takahashi D, et al. EBioMedicine. 2020 Aug;58:102913. doi: 10.1016/j.ebiom.2020.102913. Epub 2020 Jul 22. EBioMedicine. 2020. PMID: 32711255 Free PMC article. - Thymus-derived regulatory T cells contribute to tolerance to commensal microbiota.
Cebula A, Seweryn M, Rempala GA, Pabla SS, McIndoe RA, Denning TL, Bry L, Kraj P, Kisielow P, Ignatowicz L. Cebula A, et al. Nature. 2013 May 9;497(7448):258-62. doi: 10.1038/nature12079. Epub 2013 Apr 28. Nature. 2013. PMID: 23624374 Free PMC article. - Induction of Treg cells in the mouse colonic mucosa: a central mechanism to maintain host-microbiota homeostasis.
Tanoue T, Honda K. Tanoue T, et al. Semin Immunol. 2012 Feb;24(1):50-7. doi: 10.1016/j.smim.2011.11.009. Epub 2011 Dec 14. Semin Immunol. 2012. PMID: 22172550 Review.
Cited by
- The gut microbiota in thrombosis.
Khuu MP, Paeslack N, Dremova O, Benakis C, Kiouptsi K, Reinhardt C. Khuu MP, et al. Nat Rev Cardiol. 2024 Sep 17. doi: 10.1038/s41569-024-01070-6. Online ahead of print. Nat Rev Cardiol. 2024. PMID: 39289543 Review. - The interplay between gut microbiota, short-chain fatty acids, and implications for host health and disease.
Hays KE, Pfaffinger JM, Ryznar R. Hays KE, et al. Gut Microbes. 2024 Jan-Dec;16(1):2393270. doi: 10.1080/19490976.2024.2393270. Epub 2024 Sep 16. Gut Microbes. 2024. PMID: 39284033 Free PMC article. Review. - Significance of Gut Microbiota on Graves' Disease.
Chen H, Cao J, Zhang F, Xiong W. Chen H, et al. Int J Gen Med. 2024 Sep 11;17:3967-3974. doi: 10.2147/IJGM.S467888. eCollection 2024. Int J Gen Med. 2024. PMID: 39281039 Free PMC article. Review. - The Impact of Japanese Dietary Patterns on Metabolic Dysfunction-Associated Steatotic Liver Disease and Liver Fibrosis.
Sasada T, Iino C, Sato S, Tateda T, Igarashi G, Yoshida K, Sawada K, Mikami T, Nakaji S, Sakuraba H, Fukuda S. Sasada T, et al. Nutrients. 2024 Aug 28;16(17):2877. doi: 10.3390/nu16172877. Nutrients. 2024. PMID: 39275193 Free PMC article. - Gut microbiota dysbiosis and its impact on asthma and other lung diseases: potential therapeutic approaches.
Kim YC, Sohn KH, Kang HR. Kim YC, et al. Korean J Intern Med. 2024 Sep;39(5):746-758. doi: 10.3904/kjim.2023.451. Epub 2024 Aug 30. Korean J Intern Med. 2024. PMID: 39252487 Free PMC article. Review.
References
- Immunity. 2008 Apr;28(4):546-58 - PubMed
- J Biol Chem. 2007 Jun 22;282(25):18532-18541 - PubMed
- Nat Med. 2007 Nov;13(11):1299-307 - PubMed
- Cell. 1978 May;14(1):105-13 - PubMed
- J Biol Chem. 2003 Mar 28;278(13):11312-9 - PubMed
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Other Literature Sources
Research Materials